madman
Super Moderator
Controversies in Testosterone Therapy
ABSTRACT
Introduction: Testosterone prescriptions have increased dramatically in recent years, largely because of changes in expert guidelines. Concerns have been raised that testosterone therapy (TTh) may be associated with an increased incidence of conditions such as cardiovascular (CV) disease, thromboembolic events, obstructive sleep apnea (OSA), benign prostatic hyperplasia (BPH), and prostate cancer (PCa) and also may be a beneficial therapy in the management of prediabetes. As such, considerable debate remains regarding which hypogonadal populations are appropriate candidates for TTh.
Objectives: This systematic review aims to affirm or refute, using the most current evidence, the published concerns surrounding TTh and its potential increased risk of conditions such as CV disease, thromboembolic events, OSA, urolithiasis, BPH, and PCa, as well as its role as a potential tool for managing prediabetes.
Methods: A systematic review of the literature surrounding TTh and its impact on increasing risk for the adverse conditions mentioned previously was performed. 62 publications were selected for inclusion based on their relevance to the effects and risks of TTh. Evidence is current through December 2019.
Results: Evidence demonstrates that positive associations exist between TTh and OSA, erythrocytosis, as well as urolithiasis. TTh may potentially be used to treat hypogonadal men with prediabetes. While low testosterone is positively correlated with adverse CV events, TTh in hypogonadal men either has no effect or decreases such risk. TTh is likely not associated with an increased risk of PCa incidence or recurrence.
Conclusions: Despite historical beliefs that TTh increases the risk of CV disease, thromboembolic events, BPH, and PCa, recent evidence suggests that TTh conveys less risk than previously perceived. While caution should continue to be exercised, evidence suggests that TTh is a reasonable treatment option in many hypogonadal men who were previously excluded from TTh based on risk factors and prior health histories.
INTRODUCTION
Prescriptions for testosterone (T) have increased more than 3-fold between 2001 and 2011 across all age groups.1-3 The cause of this significant increase in T prescriptions is largely attributed to changes in expert guidelines, as low T has been associated with increased cardiovascular (CV) risk, and erectile dysfunction has become a part of the routine CV assessment.4
While testosterone therapy (TTh) is the primary treatment for hypogonadism, multiple studies 5,6 estimate that up to 25% of men receiving TTh do not have their T levels checked before treatment, almost 50% do not have their T levels checked after treatment and up to 33% do not meet the criteria for T deficiency. These data are further supported by a survey of nearly 250,000 American men who were treated with TTh in which only 72% had a T level measured before being prescribed TTh and only 6% had T levels measured after treatment with TTh. These data are concerning because TTh has been reported to increase the risk of conditions such as CV disease, myocardial infarction (MI), venous thromboembolism (VTE), erythrocytosis, obstructive sleep apnea (OSA), benign prostatic hyperplasia (BPH), and prostate cancer (PCa).
Following certain data about the potential risks of TTh, the United States Food & Drug Association recently required a label change which indicates that TTh may increase CV risk.7 There are several potential pathophysiological mechanisms of TTh which could account for this increased risk of CV complications. Platelet thromboxane A2 is regulated by T, which could increase platelet aggregation. TTh is often reported to induce erythrocytosis, which can theoretically thicken the blood and make it more difficult to circulate blood through the body. In addition, TTh can worsen OSA and increase vascular cell adhesion molecule 1, which can increase monocyte recruitment. Thus, it is recommended that the benefits of TTh be carefully weighed against the potential risks. Given the rapid increase in T prescriptions worldwide and the risk of adverse outcomes, recent debate has focused on which patient populations are appropriate to treat using TTh as well as the likelihood of TTh increasing risk for more serious health conditions.
This systematic review aims to affirm or refute published concerns, based on current data, regarding the impacts of TTh on increasing risk for conditions such as CV disease, MI, OSA, VTE, erythrocytosis, BPH, or PCa as well as the potential use of TTh in the management of type 2 diabetes mellitus (T2D) and prediabetes.
CLINICAL OBJECTIVES OF TTH
CONTROVERSIES IN TTH
*Diabetes
*Erythrocytosis
*Obstructive Sleep Apnea
*CV Events
*T Effects on the Prostate
*Genitourinary Impacts of T
CONCLUSION
TTh is the mainstay in hypogonadal men. Concerns regarding a potential increased risk of CV disease, MI, thromboembolic events, OSA, BPH, and the development and recurrence of PCa in men on TTh continue to be debated, although evidence suggests that TTh has a smaller impact on these conditions than initially perceived. In addition, TTh may potentially be used as an adjunct therapy in hypogonadal men with prediabetes, although data are somewhat limited on this topic and are not entirely congruent between studies.
Significant evidence now exists to suggest that TTh does not increase the risk, and may even decrease the risk, of MI, BPH, and the development of PCa. While TTh increases the risk of erythrocytosis, the clinical implications of erythrocytosis remain unclear. Recent evidence suggests that TTh is positively associated with VTE both in hypogonadal and eugonadal men, although more evidence is needed to confirm these findings. There appears to be a positive association between TTh and increased risk of OSA. Also, a recent novel association has been identified between TTh and the development of calcium oxalate urolithiasis, although additional work is needed to confirm this finding.
It appears that in many cases, TTh may be less harmful than once feared and can be more frequently used to treat hypogonadal men who were previously excluded from such therapy. However, some caution should still be exercised when administering TTh in certain populations as there is still a potential measure of increased risk for adverse outcomes.
ABSTRACT
Introduction: Testosterone prescriptions have increased dramatically in recent years, largely because of changes in expert guidelines. Concerns have been raised that testosterone therapy (TTh) may be associated with an increased incidence of conditions such as cardiovascular (CV) disease, thromboembolic events, obstructive sleep apnea (OSA), benign prostatic hyperplasia (BPH), and prostate cancer (PCa) and also may be a beneficial therapy in the management of prediabetes. As such, considerable debate remains regarding which hypogonadal populations are appropriate candidates for TTh.
Objectives: This systematic review aims to affirm or refute, using the most current evidence, the published concerns surrounding TTh and its potential increased risk of conditions such as CV disease, thromboembolic events, OSA, urolithiasis, BPH, and PCa, as well as its role as a potential tool for managing prediabetes.
Methods: A systematic review of the literature surrounding TTh and its impact on increasing risk for the adverse conditions mentioned previously was performed. 62 publications were selected for inclusion based on their relevance to the effects and risks of TTh. Evidence is current through December 2019.
Results: Evidence demonstrates that positive associations exist between TTh and OSA, erythrocytosis, as well as urolithiasis. TTh may potentially be used to treat hypogonadal men with prediabetes. While low testosterone is positively correlated with adverse CV events, TTh in hypogonadal men either has no effect or decreases such risk. TTh is likely not associated with an increased risk of PCa incidence or recurrence.
Conclusions: Despite historical beliefs that TTh increases the risk of CV disease, thromboembolic events, BPH, and PCa, recent evidence suggests that TTh conveys less risk than previously perceived. While caution should continue to be exercised, evidence suggests that TTh is a reasonable treatment option in many hypogonadal men who were previously excluded from TTh based on risk factors and prior health histories.
INTRODUCTION
Prescriptions for testosterone (T) have increased more than 3-fold between 2001 and 2011 across all age groups.1-3 The cause of this significant increase in T prescriptions is largely attributed to changes in expert guidelines, as low T has been associated with increased cardiovascular (CV) risk, and erectile dysfunction has become a part of the routine CV assessment.4
While testosterone therapy (TTh) is the primary treatment for hypogonadism, multiple studies 5,6 estimate that up to 25% of men receiving TTh do not have their T levels checked before treatment, almost 50% do not have their T levels checked after treatment and up to 33% do not meet the criteria for T deficiency. These data are further supported by a survey of nearly 250,000 American men who were treated with TTh in which only 72% had a T level measured before being prescribed TTh and only 6% had T levels measured after treatment with TTh. These data are concerning because TTh has been reported to increase the risk of conditions such as CV disease, myocardial infarction (MI), venous thromboembolism (VTE), erythrocytosis, obstructive sleep apnea (OSA), benign prostatic hyperplasia (BPH), and prostate cancer (PCa).
Following certain data about the potential risks of TTh, the United States Food & Drug Association recently required a label change which indicates that TTh may increase CV risk.7 There are several potential pathophysiological mechanisms of TTh which could account for this increased risk of CV complications. Platelet thromboxane A2 is regulated by T, which could increase platelet aggregation. TTh is often reported to induce erythrocytosis, which can theoretically thicken the blood and make it more difficult to circulate blood through the body. In addition, TTh can worsen OSA and increase vascular cell adhesion molecule 1, which can increase monocyte recruitment. Thus, it is recommended that the benefits of TTh be carefully weighed against the potential risks. Given the rapid increase in T prescriptions worldwide and the risk of adverse outcomes, recent debate has focused on which patient populations are appropriate to treat using TTh as well as the likelihood of TTh increasing risk for more serious health conditions.
This systematic review aims to affirm or refute published concerns, based on current data, regarding the impacts of TTh on increasing risk for conditions such as CV disease, MI, OSA, VTE, erythrocytosis, BPH, or PCa as well as the potential use of TTh in the management of type 2 diabetes mellitus (T2D) and prediabetes.
CLINICAL OBJECTIVES OF TTH
CONTROVERSIES IN TTH
*Diabetes
*Erythrocytosis
*Obstructive Sleep Apnea
*CV Events
*T Effects on the Prostate
*Genitourinary Impacts of T
CONCLUSION
TTh is the mainstay in hypogonadal men. Concerns regarding a potential increased risk of CV disease, MI, thromboembolic events, OSA, BPH, and the development and recurrence of PCa in men on TTh continue to be debated, although evidence suggests that TTh has a smaller impact on these conditions than initially perceived. In addition, TTh may potentially be used as an adjunct therapy in hypogonadal men with prediabetes, although data are somewhat limited on this topic and are not entirely congruent between studies.
Significant evidence now exists to suggest that TTh does not increase the risk, and may even decrease the risk, of MI, BPH, and the development of PCa. While TTh increases the risk of erythrocytosis, the clinical implications of erythrocytosis remain unclear. Recent evidence suggests that TTh is positively associated with VTE both in hypogonadal and eugonadal men, although more evidence is needed to confirm these findings. There appears to be a positive association between TTh and increased risk of OSA. Also, a recent novel association has been identified between TTh and the development of calcium oxalate urolithiasis, although additional work is needed to confirm this finding.
It appears that in many cases, TTh may be less harmful than once feared and can be more frequently used to treat hypogonadal men who were previously excluded from such therapy. However, some caution should still be exercised when administering TTh in certain populations as there is still a potential measure of increased risk for adverse outcomes.
